Human mammary epithelial antigens (HME-Ags) have been described by us as being normal differentiation breast tissue antigens present both in normal and neoplastic breast tissue. Their narrow tissue distribution allowed us to use them as histological markers for breast epithelial cells. It was also possible to detect and quantitate HME-Ags with an RIA in the circulation of breast cancer patients, but not in normal subjects or patients with non-breast cancer. On the other hand, radioactively tagged antibody fragments against HME-Ags localized simulated metastases of breast cancer, (represented by transplantable human breast tumors grafted in nude mice), by whole body scanning. Lately, with monoclonal antibodies we have created against similar breast epithelial cell surface components, we have been able to arrest breast tumor growth by 90% in nude mice. Thus, we propose: a) to perform large scale clinical trials to further substantiate the value of circulating HME-Ags and as a valuable tool in the follow-up of breast cancer and possibly as a population screening method; RIAs, employing both polyclonal anti-HME-Ags and monoclonal antibodies mentioned above, will be used to: quantitate their corresponding antigens i) in a large pool of breast cancer patients and their controls, and ii) in longitudinal studies in designated breast cancer patients; b) to optimize our breast tumor imaging procedures using Fabragments of our newly created anti-breast epithelial monoclonal antibodies; fragments of a monoclonal antibody or a mixture of several of them will be used and several new labelling procedures will be explored in studies leading to direct clinical application shortly, and c) to develop and refine our experimental approaches to the therapy of breast cancer using mixtures ("cocktails") of antibreast epithelial monoclonal antibodies. With nude mice grafted with human tumors as a model, we will explore appropriate "cocktail" composition, optional injection schedule, the use of cojugates attached to the antibodies, to enhance their tumor growth inhibition and also study the mechanisms by which monoclonal act on the breast tumors in this system.